Abstract

Analysis of CYP1B1 in primary congenital glaucoma (PCG) patientsfrom various ethnic populations indicates that allelic heterogeneity ishigh, and some mutations are population specific. No study haspreviously reported the rate or spectrum of CYP1B1 mutations inAustralian PCG patients. The aim of this study is to determine thefrequency of CYP1B1 mutations in our predominately Caucasian,Australian cohort of PCG cases. Thirty-seven probands were recruitedfrom South-Eastern Australia, along with 100 normal control subjects.Genomic DNA was extracted and the coding regions of CYP1B1analysed by direct sequencing. Sequence analysis identified 10 differentCYP1B1 disease-causing variants in eight probands (21.6%). Fivesubjects were compound heterozygotes, two subjects heterozygous andone homozygous for CYP1B1 mutations. Three missense mutations arenovel (D192Y, G329D, and P400S). None of the novel mutationsidentified were found in normal controls. One normal control subject washeterozygous for the previously reported CYP1B1 R368H mutation. Sixpreviously described probable polymorphisms were also identified.Mutations in CYP1B1 account for approximately one in five PCG casesfrom Australia. Our data also supported the high degree of allelicheterogeneity seen in similar studies from other ethnic populations,thereby underscoring the fact that other PCG-related genes remain to beidentified.